This project is designed to provide new insight into the mechanisms by which foreign DNA interacts with host chromosomal DNA. Specifically, we shall study the development of bacteriophage Mu in Escherichia coli. This virus resembles in many key features the animal DNA tumor viruses, DNA insertion sequences and DNA transposition elements. We will focus our efforts on the following points: 1. Examination of the fate of the primary Mu prophage after induction including: a. Determination of whether Mu DNA excise from its site of integration, and if so, whether it dose so with or without adjacent host sequences. b. Characterization of the physical state of any exised Mu DNA. c. Definition of the time course of any excision relative to the onset of viral DNA synthesis and to the formation of heterogeneous circular DNA (Hc-DNA). 2. Investigation of some basic parameters of Mu DNA synthesis, including: a. Definition of the time course of synthesis of Mu DNA. b. Definition of the replicative form(s) of Mu DNA. c. Analysis of in situ replication. 3. Examination of the capacity of Mu DNA to assume a circular form exclusive of host sequences. 4. Characterization of essential properties of Hc-DNA, including: a. Kinetics of appearance, particularly with respect to the time of onset of Mu DNA synthesis. b. examination of changes in the host sequences present in Hc-DNA. c. Determination of overall size changes throughout lytic cycle. d. Accumulation of Mu sequences in the population and in individual molecules. 5. Evaluation of the effects of vegetative Mu development upon the organization and integrity of host DNA.